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Molecular Signature as Optima of Multi-Objective Function with Applications to Prediction in Oncogenomics
Aligerová, Zuzana ; Maděránková, Denisa (referee) ; Provazník, Ivo (advisor)
Náplní této práce je teoretický úvod a následné praktické zpracování tématu Molekulární signatura jako optimální multi-objektivní funkce s aplikací v predikci v onkogenomice. Úvodní kapitoly jsou zaměřeny na téma rakovina, zejména pak rakovina prsu a její podtyp triple negativní rakovinu prsu. Následuje literární přehled z oblasti optimalizačních metod, zejména se zaměřením na metaheuristické metody a problematiku strojového učení. Část se odkazuje na onkogenomiku a principy microarray a také na statistiku a s důrazem na výpočet p-hodnoty a bimodálního indexu. Praktická část je pak zaměřena na konkrétní průběh výzkumu a nalezené závěry, vedoucí k dalším krokům výzkumu. Implementace vybraných metod byla provedena v programech Matlab a R, s využitím dalších programovacích jazyků a to konkrétně programů Java a Python.
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Molecular Characterisation of Parvalbumin Gene: Evolutionary Insights and Forensic Applications for Fish Species Identification and Authentication
Mukherjee, Subham ; Horká, Petra (advisor) ; Kalous, Lukáš (referee) ; Flajšhans, Martin (referee)
Abstract Parvalbumin (pvalb), a low molecular weight calcium-binding protein, plays a crucial role in regulating Ca2+ switching in fast-twitch muscle fibres and has been identified as a major cause of fish-induced food allergies. The molecular evolution of pvalb genes in teleost fish and its cause, duplication of the whole genome, was investigated, revealing high diversity and complex gene repertoires, making detection and identification challenging. This study provides robust genomic evidence of the complex evolution of parvalbumin genes in teleost fish. In addition to its role as a potent allergen, the pvalb gene, a nuclear gene, can serve as a valuable molecular marker. Keeping this in mind, a real-time PCR assay is developed to detect and quantify two European anglerfish species simultaneously, Lophius piscatorius and Lophius budegassa, which are susceptible to illegal species substitutions in the global seafood trade. The assay targets the intronic region of the pvalb gene, demonstrating high specificity, efficiency, and robustness, making it a potential forensic tool to prevent food fraud and ensure the accurate identification of fish species. Furthermore, a standardised quantitative PCR-based method is presented for the β-pvalb gene in Lophius piscatorius, utilising a plasmid DNA calibrator...
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Function of the Tetratrico-peptide Thioredoxin-Like (TTL) gene family in root system development
Xin, Pengfei ; Soukup, Aleš (advisor) ; Vaňková, Radomíra (referee) ; Ovečka, Miroslav (referee)
The root system performs fundamental plant functions such as uptake of nutrients and water, anchoring in the substrate, and interacting with the rhizosphere abiotic and biotic interactions, playing an important role in meeting the food security needs of today's world. Lateral roots (LR) are essential components of the plant root system. We have identified the TETRATRICOPEPTIDE-REPEAT THIOREDOXIN- LIKE 3 (TTL3) gene as being related to LR emergence and later development. Loss-of-function of TTL3 results in a reduced number of emerging LRs due to delayed development of lateral root primordia (LRP). In the Arabidopsis TTL gene family, except for TTL2 which was specifically involved in male gametophyte development, the expressions of the other three TTLs (TTL1, TTL3 and TTL4) were all related to root growth and development. The temporal and spatial distribution of TTL3 expression was consistent with its role in LR growth preceding and following LRP emergence. In the subcellular localization of TTL1, TTL2 and TTL3, all were shown to be associated with microtubules during the transient transformation of tobacco leaves, and TTL3 was confirmed to interact with microtubules. TTL3 was also associated with the endomembrane system and was known to be interacting with the brassinosteroid (BR) signaling pathway....
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Functional analysis of posttranscriptional gene regulation by TENT5A in biomineralization and metabolism
Aranaz Novaliches, Goretti ; Sedláček, Radislav (advisor) ; Hovořáková, Mária (referee) ; Tencerová, Michaela (referee)
Non-canonical poly-A polymerases, such as TENT5A, belong to the Terminal nucleotidyl transferases (TENTs) family and are crucial for mRNA protection, stability, and translation. A Tent5a knock-out (KO) mouse model was generated in our laboratory, which exhibited a phenotype in teeth, skeleton structure, and metabolism. In my PhD project, I aimed to characterize the molecular mechanism underlying these phenotypes and explore their potential connection to rare human diseases. I focused on the biological function of Tent5a gene in enamel development (amelogenesis) and mRNA stabilization. Micro-computed tomography and scanning electron microscopy revealed that Tent5a KO mice displayed thin, hypomineralized enamel with disrupted microstructure, a condition known as Amelogenesis imperfecta. Direct mRNA sequencing demonstrated that TENT5A is responsible for polyadenylation of amelogenin (AmelX) and other secreted proteins, leading to a shortened poly-A tail in Tent5a KO ameloblasts. Moreover, Tent5a KO mice disclosed impaired self- assembly of enamel matrix proteins (EMPs) such as AMELX and ameloblastin (AMBN), leading to compromised hydroxyapatite deposition and enamel formation. In addition to its role in teeth, I investigated the physiological functions of EMPs in other tissues, considering that EMP...
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Clinical significance of the rs4646994 polymorphism in the ACE gene
BÍCHOVÁ, Simona
The present bachelor thesis deals, as it is obvious from the title, with one particular polymorphism rs4646994 in the ACE gene and its clinical significance. The ACE gene, consisting of 26 exons, is localized on chromosome 17q23 and its name ACE stands for angiotensin converting enzyme. This enzyme is capable of breaking down proteins and is part of the renin-angiotensin system, which regulates blood pressure and fluid and salt balance in the body. The principle is to split a protein called angiotensin I into angiotensin II. This then causes the blood vessels to narrow (constrict), leading to an increase in blood pressure. This protein also stimulates the production of the hormone aldosterone, which triggers the absorption of salts and water by the kidneys. The increased amount of fluid in the body subsequently increases blood pressure. In addition, angiotensin II may also play a role in kidney development. The selected ACE rs4646994 polymorphism is of great interest in terms of various diseases (e.g. COVID-19, nephropathy in diabetes mellitus, polycystic ovary syndrome, etc.) It may also play an important role in Alzheimer's disease, which is the focus of the practical part of this bachelor thesis. The investigation of the rs4646994 polymorphism in the ACE gene was carried out in a selected group of 61 patients with a diagnosis of dementia by end-point PCR. The data obtained were then statistically processed and compared with a control group of patients without a diagnosis of dementia. The results were then compared with available scientific publications.
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Determination of tick-pathogen interactions during acquisition and transmission of Borrelia duttonii by Ornithodoros moubata
ĆETKOVIĆ, Ana
The goal of this thesis was to investigate the interaction between Borrelia duttonii, a causative agent of TBRF in Africa, and its tick vector Ornithodoros moubata in terms of acquisition and transmission dynamics. The infectivity of frozen sera and infected unfed O. moubata ticks was evaluated. The acquisition efficiency of B. duttonii 1120K3 and Ly isolates by O. moubata was determined and compared. The minimum acquisition time was established as well. Moreover, the sensitivity of Borrelia in the presence of different animal sera was analysed.
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Gene regulatory network inference based on mutual information in non-model organisms
Pirkl, Petr ; Sedlář, Karel (referee) ; Musilová, Jana (advisor)
The thesis is focused on summary of laboratory methods for determining gene expression, data preprocessing procedures and possible tools used to infere gene regulatory networks. Furthermore, the thesis handles with the pre-processing of data. It means create count table and normalize it. It was use data from the non-model organism Clostridium beijerinckii NRRL B-598. The main parts of the thesis are designed an algorithm for the creation of a gene regulatory network using mutual information and its implementation in the R language. This include testing the algorithm on data from the non-model organism and the gold standard.
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The role of vent genes family in early development and brain development
Fabian, Peter ; Kozmík, Zbyněk (advisor) ; Němec, Pavel (referee) ; Balaštík, Martin (referee)
6 III ABSTRACT (ENGLISH) In chordates, the central nervous system (CNS) is derived from the dorsal part of gastrula. Induced dorsal part of the embryo - the neural plate - gives rise to the neural tube or primordial brain. The developing dorsal part of the embryo is shaped by BMP/Smad signaling from the ventral part. Using the basal chordate amphioxus, we show here the conserved evolutionary role BMP/Smad signaling in axial cell fate determination. Pharmalogical inhibition of BMP/Smad signaling induces dorsalization of Branchiostoma floridae (amphioxus) and Oryzias latipes (medaka) embryos and expansion of neural plate markers. We provide evidence for the presence of the positive regulatory loop within the BMP/Smad signaling network of amphioxus. Thus, our data suggest that early emergence of a positive feedback loop within the BMP/Smad signaling network may represent a crucial molecular event in the evolutionary history of the chordate cell fate determination. The dorso-ventral body axis formation is mediated by genes of the vent family, which are the direct targets of BMP/Smad signaling. The function of vent gene family in early development is relatively well known, however, its role in developing CNS is not yet clear. Therefore, we decided to manipulate vox transcription factor, a vent family member....
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The Influence of Specific Genes on Joint Hypermobility
Krýda, Tomáš ; Žatečka, Ladislav (advisor) ; Tomší, Adéla (referee)
This thesis is concerned with the influence of specific genes on the occurence of joint hypermobility. The main goal is to verify, whether the hypermobility test results differ among persons tested for the polymorphism of COL5A1, ACTN3, COL1A1 and GDF-5 gene with the respet to a particular genotype. The theoretical part of the thesis presented the specifics of sports genetics, general overview of the most important findings about hypermobilty, the manners in which it can be examined, its clinical features and also a detailed analysis of the role of the above stated genes, their association with health and performance attributes and their relation to hypermobility and range of motion. In the practical part, an examination of 15 probands (9 males and 6 females) at the age of 28,7 ± 5,6 years was conducted applying four scoring systems for measuring hypermobility. All probands were genetically tested by the PCR method. The statistical analysis was carried out by one-factor ANOVA. The statistical significance p < 0,05 wasn't reached with respect to any of the analysed genes. For SNP rs 12722 of COL5A1 gene, the average medians of the total hypermobilty score with respect to a particular genotype were 10,82 (CC), 7,30 (CT) and 10,99 (TT). For SNP rs 1815739 of ACTN3 the average medians of the total...
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Immunogenetic and hormonal markers of predisposition to systemic rheumatic diseases particularly systemic lupus erythematosus
Fojtíková, Markéta ; Pavelka, Karel (advisor) ; Hrnčíř, Zbyněk (referee) ; Rovenský, Jozef (referee)
Fojtikova 2011 INTRODUCTION: Several factors like genetic susceptibility is required for systemic rheumatic diseases development. Immunomodulatory PRL effect supports autoimmunity. AIMS: 1. To detect the immunogenetic background (alleles HLA class I, II and microsatellite polymorphism of the transmembrane part exon 5 of MIC-A gene) of SLE and PsA. 2. To detect PRL serum and synovial fluid with regard to clinical and laboratory RA activity. 3. To find the role of the functional polymorphism -1149G/T SNP PRL of extrapituitary promoter of PRL gene in SLE, RA, PsA, SSc and inflammatory myopathies development. METHODS: Genetic analyses of pateints with SLE (n=156), RA (n=173), PsA (n=100), SSc (n=75), PM (n=47) a DM (n=68) and 123 healthy individuals: PCR-SSP (HLA clase I and II), PCR-fragment analysis (MIC-A) a PCR-RFLP (-1149 G/T SNP PRL). In 29 RA a 26 OA PRL serum and synovial fluid concentrations were detected using immunoradiometric assay. RESULTS: 1. The allele HLA-DRB1*03 (pc=0.008; OR 2.5) and haplotype HLA-DRB1*03-DQB1*0201 (pc <0.001; OR 4.54) were determined as risk immunogenetic markers for SLE in Czech population. In SLE versus controls allele MIC-A5.1 was increased (pc =0.005; OR 1.88). MIC-A5.1 together with HLA-DRB1*03 increases the risk for SLE development, pc <0.000001; OR 9.71....
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